Anti-proliferative and pro-apoptotic effects of lichen-derived compound protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity.

Abstract

Lipoxygenases (LOXs) and their products are involved in several biological functions and have been associated with carcinogenesis. Protolichesterinic acid (PA), a lichen metabolite, inhibits 5- and 12-LOX and has anti-proliferative effects on various cancer cell lines. Here, PA was shown to inhibit proliferation of multiple myeloma cells, RPMI 8226 and U266, and pancreatic cancer cells AsPC-1. Apoptosis was induced only in multiple myeloma cells. Cell-cycle associated changes in expression and sub-cellular localization of 5- and 12-LOX were not affected by PA but increased cytoplasmic localisation was found to accompany morphological changes at later stages. Assessment by mass spectrometry showed that PA entered the pancreatic cancer cells. However, effects on LOX metabolites were only evident after treatment with concentrations exceeding those having anti-proliferative effects and no effects were measurable in the myeloma cells. We conclude that the anti-proliferative and pro-apoptotic effects of PA are not mediated directly through inhibition of LOX activity.

• Authors: M Bessadóttir, F F Eiríksson, S Becker, M H Ögmundsdóttir, S Ómarsdóttir, M Thorsteinsdóttir, H M Ögmundsdóttir
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 98 Pg. 39-47 (Jul 2015) ISSN: 1532-2823 [Electronic] Scotland
• PMID: 25964147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• protolichesterinic acid
• Arachidonate 12-Lipoxygenase
• ALOX12 protein, human
• Arachidonate 5-Lipoxygenase
• ALOX5 protein, human
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, pharmacology)
• Apoptosis
• Arachidonate 12-Lipoxygenase (metabolism)
• Arachidonate 5-Lipoxygenase (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytoplasm (enzymology)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lichens (chemistry)
• Multiple Myeloma (drug therapy, enzymology)
• Pancreatic Neoplasms (drug therapy, enzymology)